The long term objectives of this proposal are to understand the mechanisms which regulate gene expression and the ways in which gene expression affects development and behavior. We propose to study this problem in one experimental organism, Drosophila melanogaster, because of the wealth of genetic information, procedures, and existing or readily obtainable variants connected with this organism. Also, the recent advent of DNA-mediated transformation makes it now possible to examine the relationship between specific DNA sequence and gene expression or phenotype, in a manner unparalleled in any other complex metazoan. (i) We will clone the per gene, involved in the determination or maintenance of biological rhythms. This gene will be characterized from molecular, phenotypic, and evolutionary perspectives in order to understand how a single gene has such a complex effect on different biorhythms. (ii) We will utilize cloned genes to improve current procedures to generate genetic mosaics in Drosophila. Successful completion of this project will allow the undertaking of experiments that are almost impossible with existing techniques, (iii) We will analyze the way in which Drosophila controls the expression of its four alpha-tubulin genes. This will be pursued by exchanging regions and sub-regions of alpha-tubulin genes and examining the pattern of expression of these altered genes subsequent to DNA-mediated transformation into the Drosophila germ line. (iv) We will study the genetics plus molecular biology of the vnd and kp loci and their control of neurogenesis in Drosopila embryos. (v) We will pursue genetic and molecular experiments to characterise further the structure and possible function of the complex embryonic transcripts, which are coded for by chromosome region 99D. We will also undertake a study to define the number, location, and properties of open reading frame DNA segments in Drosophila. These five projects will be performed in an interactive fashion so that each of the laboratories will be able benefit from the individual project investigations, in proper program project fashion.